Thrombolytic therapy in acute venous thromboembolism.

Although anticoagulation remains the mainstay of treatment of acute venous thromboembolism (VTE), the use of thrombolytic agents or thrombectomy is required to immediately restore blood flow to thrombosed vessels. Nevertheless, systemic thrombolysis has not clearly been shown to improve outcomes in patients with large clot burdens in the lung or legs as compared with anticoagulation alone; this is in part due to the occurrence of intracranial hemorrhage in a small percentage of patients to whom therapeutic doses of a thrombolytic drug are administered. Algorithms have been developed to identify patients at high risk for poor outcomes resulting from large clot burdens and at low risk for major bleeding in an effort to improve outcomes in those receiving thrombolytic therapy. In acute pulmonary embolism (PE), hemodynamic instability is the key determinant of short-term survival and should prompt consideration of immediate thrombolysis. In hemodynamically stable PE, systemic thrombolysis is not recommended and should be used as rescue therapy if clinical deterioration occurs. Evidence is accumulating regarding the efficacy of administering reduced doses of thrombolytic agents systemically or via catheters directly into thrombi in an effort to lower bleed rates. In acute deep venous thrombosis, catheter-directed thrombolysis with thrombectomy can be used in severe or limb-threatening thrombosis but has not been shown to prevent postthrombotic syndrome. Because the management of acute VTE can be complex, having a rapid-response team (ie, PE response team) composed of physicians from different specialties may aid in the management of severely affected patients.

Prevalence and Mortality of Venous Leg Diseases of the Deep Veins: An Observational Cohort Study Based on German Health Claims Data.

This study estimates the prevalence and mortality of diseases of the deep veins of the legs such as deep vein thrombosis (DVT), postthrombotic syndrome (PTS), and venous leg ulceration (VLU). We used a random sample of 250 000 patients at age 50+ years of the register of the Allgemeine Ortskrankenkasse from 2004 to 2015. Selected manifestations of venous diseases assumed as risk factors for mortality were analyzed using Cox models while adjusting for various basic demographic and health characteristics. The prevalence in 2004 was 0.05% for DVT of the femoral veins, 0.50% for DVT of any deep veins, 0.86% for PTS, and 0.91% for VLU. The mortality rate in 2004 to 2015 was 20.40 deaths/100 person-years for DVT of the femoral veins, 10.69 for DVT of any deep veins, 4.34 for PTS, and 7.02 for VLU. The model revealed a 35% higher risk (p < .001) in patients with any DVT, an 88% higher mortality (p < .001) for femoral DVT, a 23% higher risk (p < .001) for VLU, and no health disadvantage in persons with PTS. Our study revealed an increased mortality for patients with VLU and DVT. Even after adjustment for embolic events and infections of the venous ulcers mortality remained significantly higher.

Ultrasound-Accelerated Thrombolysis and Venoplasty for the Treatment of the Postthrombotic Syndrome: Results of the ACCESS PTS Study.

Background Postthrombotic syndrome is a common complication of deep vein thrombosis, with limited treatment options. Methods and Results ACCESS PTS (Accelerated Thrombolysis for Post-Thrombotic Syndrome Using the Acoustic Pulse Thrombolysis Ekosonic Endovascular System) is a multicenter, single-arm, prospective study evaluating patients with chronic deep vein thrombosis and postthrombotic syndrome (Villalta score ≥8) who received minimum 3 months of anticoagulation. Patients underwent percutaneous transluminal venoplasty and ultrasound-accelerated thrombolysis, with data collected on clinical characteristics, postthrombotic syndrome, imaging, and quality of life to 1 year. The primary efficacy outcome was a reduction of ≥4 points in the Villalta score 30 days after procedure. The primary safety outcomes were major bleeding episodes within 72 hours and symptomatic pulmonary embolism during the index hospitalization. A total of 82 limbs (78 patients) were treated (age, 54.6±12.7 years; 32.1% women; mean Villalta score, 15.5±5.2). The primary end point was met in 64.6% (51/79). At 1 year, 77.3% (51/66) of limbs continued with a Villalta reduction ≥4. At 365 days, >90% of segments had patency with ultrasound flow present. Baseline to 1-year Physical Component Summary mean score of the Short Form-36 increased from 38.9±9.5 to 45.2±9.8 (P≤0.0001), and mean VEINES-QOL (Venous Insufficiency Epidemiological and Economic Study-Quality of Life) increased from 61.9±19.7 to 82.6±20.8 at 1 year (P<0.0001). Iliofemoral venous stenting was performed in 42 patients, with similar improvements seen in all outcomes, regardless of stenting status. One patient developed severe bleeding within 72 hours of the intervention and died at 32 days after procedure (1.3% mortality rate). Conclusions Percutaneous transluminal venoplasty and ultrasound-accelerated thrombolysis resulted in successful recanalization of chronic venous obstruction with improved postthrombotic syndrome severity and quality of life. Results were sustained at 1-year after procedure. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02159521.

Obesity Paradox in Patients With Deep Venous Thrombosis.

We aimed to investigate the association between obesity and deep venous thrombosis (DVT) in a country with a high prevalence of obesity. This is a retrospective cohort study of patients who presented with DVT between 2008 and 2012. Data were analyzed and compared based on body mass index (BMI), and patients were classified into normal (<25), overweight (≥25 to <30), obese I (30 to <35), obese II (35 to <40), and obese III (≥40). Among 662 patients with DVT, 28% were overweight and 49% were obese. The mean age was 50.3 (16.5) years, and 51% were females. Diabetes mellitus and prior venous thromboembolism were significantly higher among obese patients. History of malignancy was more common in nonobese patients. Protein S and antithrombin III deficiency and hyperhomocysteinemia were more prevalent among morbid obese patients. Also, obese patients had higher incidence of thrombosis in the distal veins ( P = .03). Warfarin use and long-term therapy were more frequent in obese than nonobese. Postthrombotic syndrome was comparable in obese and nonobese groups. Recurrent DVT was higher in obese I ( P < .01), whereas mortality rates were greater in nonobese groups ( P = .001). Malignancy, diabetes mellitus, and common femoral vein involvement were predictors of mortality, whereas BMI ≥30 was the predictor of survival. Cox regression models showed that after adjusting for age, sex, pulmonary embolism, and duration of warfarin treatment, BMI ≥40 had better survival (hazard ratio: 0.177, 95% confidence interval: 0.045-0.691, P = .013). There is a significant association between obesity and DVT. Obese patients have characteristic risk factors and better survival. This obesity paradox needs further studies to assess its clinical and pharmacotherapeutic implications.

Chronic complications of venous thromboembolism.

Venous thromboembolism (VTE) is a common disease (~700 per 100 000) that is associated with significant risk of recurrence, chronic complications, and substantial mortality, with reported death rates of up to 40% at 10 years. The development of novel anticoagulants has revolutionized the treatment of acute VTE, while strategies for prevention and treatment of chronic complications still seek for such a landmark change. Impaired thrombus resolution is the common denominator behind VTE complications, which are postthrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (CTEPH). PTS and CTEPH are associated with substantial morbidity and high healthcare expenses. While PTS occurs in up to 50% of patients after symptomatic deep vein thrombosis, only a small and poorly defined number of patients are diagnosed with CTEPH after pulmonary embolism. This review is a comprehensive summary of VTE-related chronic complications, their epidemiology, diagnosis, and treatment.

Chronic Complications After Femoral Central Venous Catheter-related Thrombosis in Critically Ill Children.

Prescription of thromboprophylaxis is not a common practice in pediatric intensive care units. Most thrombi are catheter-related and asymptomatic, without causing acute complications. However, chronic complications of these (a)symptomatic catheter-related thrombi, that is, postthrombotic syndrome (PTS) and residual thrombosis have not been studied. To investigate these complications, critically ill children of 1 tertiary center with percutaneous inserted femoral central venous catheters (FCVCs) were prospectively followed. Symptomatic FCVC-thrombosis occurred in 10 of the 134 children (7.5%; 95% confidence interval [CI], 2.4-9.5). Only FCVC-infection appeared to be independently associated (P=0.001) with FCVC-thrombosis. At follow-up 2 of the 5 survivors diagnosed with symptomatic thrombosis developed mild PTS; one of them had an occluded vein on ultrasonography. A survivor without PTS had a partial occluded vein at follow-up. Asymptomatic FCVC-thrombosis occurred in 3 of the 42 children (7.1%; 95% CI, 0.0-16.7) screened by ultrasonography within 72 hours after catheter removal. At follow-up, mild PTS was present in 6 of the 33 (18.2%; 95% CI, 6.1-30.3) screened children. Partial and total vein occlusion was present in 1 (3%) and 4 (12%) children, respectively. In conclusion, children on pediatric intensive care units are at risk for (a)symptomatic FCVC-thrombosis, especially children with FCVC-infection. Chronic complications of FCVC-thrombosis are common. Therefore, thromboprophylaxis guidelines are warranted in pediatric intensive care units to minimize morbidity as a result of FCVC-thrombosis.

The impact of residual thrombosis on the long-term outcome of patients with deep venous thrombosis treated with conventional anticoagulation.

The impact of residual vein thrombosis (RVT) on the long-term outcome of patients with deep vein thrombosis (DVT) is unknown. We assessed the incidence of recurrent venous thromboembolism (VTE), postthrombotic syndrome (PTS), arterial thrombotic events, and cancer in patients with DVT with and without RVT. For this purpose, we evaluated up to 3 years 869 consecutive patients with acute proximal DVT who had conventional anticoagulation. RVT, defined as ultrasound incompressibility of at least 4 mm in the common femoral and/or the popliteal vein after 3 months, was detected in 429 (49.4%) patients, and was more likely in males (adjusted odds ratio [OR], 1.82; 95% confidence interval [CI], 1.37-2.04), in patients with previous VTE (OR, 1.64; 95% CI, 1.06-2.54), and in those with extensive thrombosis (OR, 3.58; 95% CI, 2.19-5.86). During the 3-year follow-up, recurrent VTE developed in 84 (19.6%) patients with RVT and 43 (9.8%) patients without RVT (adjusted hazard ratio [HR], 2.03; 95% CI, 1.40-2.94); PTS in 225 (52.4%) and 118 (26.8%), respectively (HR, 2.34; 95% CI, 1.87-2.93); arterial thrombosis in 29 (6.7%) and 14 (3.2%), respectively (HR, 2.05; 95% CI, 1.08-3.88); and cancer in 21 (4.9%) and 8 (1.8%), respectively (HR, 3.09; 95% CI, 1.31-7.28). In conclusion, in patients treated with vitamin K antagonists for prevention of recurrent VTE, RVT doubles the risk of recurrent VTE, PTS, arterial thrombosis, and cancer. Males, patients with previous VTE, and those with extensive thrombosis are independent risk factors of RVT development. Studies addressing the impact of the novel direct anticoagulants on the development of RVT as well as the long-term complications of DVT are needed.

Epidemiology, risk factors and sequelae of venous thromboembolism.

The aim of this review was to discuss the epidemiology, risk factors and sequelae of venous thromboembolism (VTE). VTE has an incidence of 1-2 per 1000 people annually. The risk of VTE increases with age and is highest in Caucasians and African Americans. Combined oral contraceptives (COC), especially the third-generation COCs, have been strongly implicated in VTE. Hospitalized patients, especially patients with underlying malignancy and undergoing surgery, have a host of risk factors for VTE. Thrombophilia can predispose an individual to VTE but indiscriminate testing for thrombophilia in patients presenting with VTE is not indicated. VTE can have serious chronic sequelae in the form of post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (CTPH). The risk of PTS and CTPH is increased with recurrent deep vein thrombosis and pulmonary embolism, respectively. Mortality from VTE can be as high as 21.6% at one year. Patients who had an episode of VTE have a high risk of subsequent VTE and this risk is highest in patients who had a first VTE event associated with malignancy. A good understanding of the epidemiology and risk factors of VTE will enable the treating medical practitioners to identify patients at risk and administer appropriate VTE prophylaxis to prevent the long-term consequences of VTE.

Current and future management of pediatric venous thromboembolism.

Venous thromboembolism (VTE) is an increasingly common complication encountered in tertiary care pediatric settings. The purpose of this review is to summarize the epidemiology, current and emerging pharmacotherapeutic options, and management of this disease. Over 70% of VTE occur in children with chronic diseases. Although they are seen in children of all ages, adolescents are at greatest risk. Pediatric VTE is associated with an increased risk of in-hospital mortality; recurrent VTE and post-thrombotic syndrome are commonly seen in survivors. In recent years, anticoagulation with low molecular weight heparin has emerged as the mainstay of therapy, but compliance is limited by its onerous subcutaneous administration route. New anticoagulants either already approved for use in adults or in the pipeline offer the possibility of improved dose stability and oral routes of administration. Current recommended anticoagulation course durations are derived from very limited case series and cohort data, or extrapolations from adult literature. However, the pathophysiologic underpinnings of pediatric VTE are dissimilar from those seen in adults and are often variable within groups of pediatric patients. Clinical studies and trials in pediatric VTE are underway which will hopefully improve the quality of evidence from which therapeutic guidelines are derived.

Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality.

Venous thromboembolism (VTE) is often asymptomatic, mis-diagnosed, and unrecognized at death, and there is a lack of routine postmortem examinations. These factors are thought to result in marked underestimates ofVTE incidence. The objective of our study was to estimate the total burden of VTE within the European Union (EU) per annum. An epidemiological model was constructed to estimate the number of community- and hospital-acquired incidents and recurrent cases (attack rate) of nonfatal VTE and VTE-related deaths, as well as incident and prevalent cases of post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (PH) occurring in the EU per annum. Individual models were developed for six EU countries. The models were populated with data from published literature and, where necessary, expert opinions. The findings were tested using probabilistic sensitivity analyses. The estimated total number of symptomaticVTE events (range based on probabilistic sensitivity analysis) per annum within the six EU countries was 465,715 (404,664-538,189) cases of deep-vein thrombosis, 295,982 (242,450-360,363) cases of pulmonary embolism (PE), and 370,012 (300,193-483,108) VTE-related deaths. Of these deaths, an estimated 27,473 (7%) were diagnosed as being antemortem; 126,145 (34%) were sudden fatal PE, and 217,394 (59%) followed undiagnosed PE. Almost three-quarters of all VTE-related deaths were from hospital-acquired VTE. VTE is a major health problem in the EU, with over one million VTE events or deaths per annum in the six countries examined. Given the availability of effective VTE prophylaxis, many of these events and deaths could have been prevented. These results have important implications for the allocation of healthcare resources.